Chelation therapy is a promising approach to mitigating health risks associated with toxic metal exposure, which contributes to cardiovascular disease, neurotoxicity, and other chronic conditions. disodium ethylene diamine tetraacetic acid (EDTA) is widely used, but its optimal dosing strategy remains unclear. This study evaluates the dose-dependent efficacy of EDTA in mobilizing toxic metals, including lead (Pb), cadmium (Cd), and gadolinium (Gd), while minimizing the loss of essential metals like copper (Cu) and manganese (Mn) to optimize therapeutic safety and efficacy. Ten volunteers (≥50 years) received 3 infusions at doses of 0.5, 1, and 3 g of EDTA over 30 min, 1 h, and 3 h, respectively. Urine and blood samples were analyzed pre- and post-infusion to assess pharmacokinetics of metal chelation. Urinary Pb excretion increased by 2200% at 0.5 g, with only a marginal gain at higher doses (3300%), supporting low-dose EDTA efficacy. Urinary Cd clearance required 3 g EDTA due to its strong tissue binding. Notably, Gd excretion increased by up to 78 000% even at 0.5 g EDTA, highlighting EDTA's potential to reduce long-term Gd burden post-MRI. Urinary excretion of essential metals varied, with Mn and Zn loss increasing at higher EDTA doses, underscoring the need for dose optimization while Cu and Ca only showed a clear increase urinary excretion at 3 g EDTA. Overall, a 0.5 g EDTA dose effectively mobilized Pb and Gd while minimizing essential metal depletion, reducing infusion time to 30 min, and improving patient compliance. These findings align with TACT and TACT 2 studies, reinforcing EDTA's long-term benefits in Pb reduction and supporting low-dose EDTA as a safe, efficient, and well-tolerated detoxification strategy.

Long-term exposure to Cd through contaminated food can lead to multiple adverse health effects on humans. Although previous studies have covered global food Cd concentrations and dietary Cd exposures across different populations, there are increasing concerns regarding the adequacy of current food Cd safety standards to protect populations from adverse health effects. Moreover, incorporation of Cd relative bioavailability (Cd-RBA) in foods improves the accuracy of health risk assessment. However, factors influencing food Cd-RBA have not been systematically discussed, thereby hindering its application in risk assessment. This review aims to provide an overview of Cd contents in foods, discuss concerns regarding international food Cd concentration standards, explore factors influencing food Cd bioavailability, and highlight the opportunities and challenges in refining differences between dietary Cd intakes and body burdens. Our findings suggest that current safety standards may be insufficient to protect human health, as they primarily focus on kidney damage as the protective endpoint and fail to account for global and regional variations in food consumption patterns and temporal changes in dietary habits over time. Factors such as crop cultivars and food compositions greatly influence food Cd-RBA. To improve the accuracy of Cd health risk assessment, future studies should incorporate food Cd-RBA, sociodemographic characteristics, nutritional status, and incidental Cd exposure. This review highlights new insights into food Cd safety standards and Cd bioavailability, identifies critical knowledge gaps, and offers recommendations for refining health risk assessments. This information is essential to inform future bioavailability investigations, health risk assessment, and safety standard development.

Cadmium (Cd(II)) is highly toxic to humans and the environment. Therefore, efficient monitoring and control of Cd(II) is required for environmental protection and human security. Over the years, impressive advances have been made, however, majority of the research focuses on either detection or removal. Herein, a novel magnetic coordination polymer gel, CoFe2O4@Zrtdpa, is explored for the twin objectives of dual mode trace Cd(II) determination and removal from real samples. Box-Behnken design combined genetic algorithm and Taguchi L32 (46 21) design optimized the removal and extraction process variables, respectively. The experimental adsorption capacity at saturation was 179.07 mg g-1 at 298 K. The uptake of Cd(II) was multimolecular (n > 1), endothermic and spontaneous. XPS revealed that two active sites were oxygen and sulphur. The adsorption energies (E1 = 41.79-46.00 kJ mol-1, E2 = 29.85-32.19 kJ mol-1) indicated that complexation at the first and electrostatic interaction through ion exchange at the second active site are at play. Density functional theory (DFT) calculations verified the same asserting that the uptake was more favorable onto the first active site (sulphur). The best fit fractal like pseudo second order model and site energy distribution analysis established energetic heterogeneity. The limits of detection (LODs) and limits of quantifications (LOQs) for the enrichment-spectrophotometric and ICP-AES methods were 1.36 μg L-1, 4.11 μg L-1, and 0.019 μg L-1, 0.062 μg L-1 respectively. The developed adsorption, enrichment-spectrophotometric and ICP-AES methods were successfully employed for the removal and trace Cd(II) determination in real samples with good reusability.

Chronic exposure to the pollutant cadmium (Cd) is inevitable for most people because it is present in nearly all food types. Concerningly, the risk of developing hypertension has been linked to dietary Cd exposure lower than 58 µg/day for a 70 kg person. The mechanisms involved are, however, unclear. Since the kidneys play an indispensable role in long-term blood pressure regulation, and they are also the main site of Cd accumulation and toxicity, a retrospective analysis was conducted to examine if kidney damage and malfunction, reflected by urinary β2-microglobulin excretion (Eβ2M), and the estimated glomerular filtration rate (eGFR), are related to Cd excretion (ECd) and blood pressure variation. Data were obtained from 689 Thai Nationals without diabetes or occupational exposure to Cd, of which 32.4% had hypertension and 7.3% had β2-microglobulinuria, defined as an increase in the β2M excretion rate ≥ 300 µg/g creatinine. Respective prevalence odds ratio (POR) and 95% confidence interval (CI) values for β2-microglobulinuria and hypertension were 10.7 (1.36-83.4), p = 0.024 and 2.79 (1.60-4.87) p < 0.001, comparing the top quartile of ECd with the bottom quartile. Only in subjects with eGFR below 90 mL/min/1.73 m2 did systolic blood pressure (SBP) and diastolic blood pressure (DBP) both increase linearly with Eβ2M (respective β = 0.182 and 0.192 for SBP and DBP) after adjustment for age, body mass index, gender, and smoking. The present study confirms the significant impact of Cd on the risk of having hypertension, following GFR loss induced by Cd. A simple mediation model analysis for cause-effect inference has provided, for the first time, evidence that may link rising SBP and DBP in Cd-exposed people to a novel role of β2M as a predictor of blood pressure variability.

Heavy metals (HMs) are hazardous contaminants with persistence and bioaccumulation, attracting widespread attention. Wastewater treatment plants (WWTPs) play vital roles in the pollution control of sewage, closely related to human health and the biological environment. Therefore, eight HMs in three typical WWTPs of Nanjing were determined in this study. The results revealed that Cr, Ni, Cu, and Zn were high-level HMs in all WWTPs. Notably, the highest contents of high-level HMs were found in electroplating WWTP (EWWTP) influent among three WWTPs, probably causing their higher removal (19.34-55.32%) during their primary treatment. In contrast, most HMs could be removed in the secondary treatment stage of municipal WWTP (MWWTP) and industrial WWTP (IWWTP) with the highest removal of As (72.00-85.81%). Analogously, nutrients were mainly removed during the secondary stage, with superior performance in MWWTP. A decrease in HMs removal was observed in the tertiary treatment of MWWTP and IWWTP compared to the secondary stage, while higher HMs removal (0.51-29.15%) was found in EWWTP except Hg. The highest content of HMs in sludge was Zn and Cr, which was more abundant in EWWTP than other WWTPs. The results of Illumina Miseq sequencing demonstrated the inhibition of microbial richness and diversity of EWWTP and IWWTP by industrial wastewater. Besides, alterations of microbial community structure and components were also observed owing to various influent sources. More similarity was found between EWWTP and MWWTP, in which the abundance of dominant genera, including Saccharimonadales (7.60-9.56%), Raineyella (5.06-7.38%), and Thauera (2.48-4.45%) was much higher than IWWTP.

Chronic kidney disease (CKD) is now the world's top seventh cause of death from a non-communicable disease, and its incidence is projected to increase further as its major risk factors, including obesity, diabetes, hypertension, and non-alcoholic fatty liver disease (NAFLD), continue to rise. Current evidence has linked the increased prevalence of CKD, diabetes, hypertension, and NAFLD to chronic exposure to the metal pollutant cadmium (Cd). Exposure to Cd is widespread because diet is the main exposure route for most people. Notably, however, the health risk of dietary Cd exposure is underappreciated, and the existing tolerable exposure guidelines for Cd do not afford health protection. New health-protective exposure guidelines are needed. From one's diet, Cd is absorbed by the intestinal epithelium from where it passes through the liver and accumulates within the kidney tubular epithelial cells. Here, it is bound to metallothionine (MT), and as it is gradually released, it induces tubular damage, tubulointerstitial inflammation and fibrosis, and nephron destruction. The present review provides an update on our knowledge of the exposure levels of Cd that are found to be associated with CKD, NAFLD, and mortality from cardiovascular disease. It discusses the co-existence of hypertension and CKD in people environmentally exposed to Cd. It highlights nuclear and mitochondrial targeting and zinc deficiency as the universal cytotoxic mechanisms of Cd. Special emphasis is placed on the novel antioxidative function of zinc involving de novo heme biosynthesis and the induced expression of heme oxygenase-1 (HO-1). Other exogenous biomolecules with promising anti-Cd toxicity are highlighted.

Exposure to low-dose environmental pollutant cadmium (Cd) increases the risks of both albuminuria and hypertension by mechanisms which are poorly understood. Here, multiple regression and mediation analyses were applied to data from 641 Thai subjects of whom 39.8%, 16.5%, 10.8%, and 4.8% had hypertension, albuminuria, diabetes, and chronic kidney disease (CKD), defined as the estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2, respectively. To correct for interindividual differences in urine dilution and surviving nephrons, the excretion rates of Cd (ECd), albumin (Ealb), and β2-microglobulin (Eβ2M) were normalized to the creatinine clearance (Ccr) as ECd/Ccr, Ealb/Ccr, and Eβ2M/Ccr. The respective risks of having CKD and hypertension rose to 3.52 (95% CI: 1.75, 7.05) and 1.22 (95% CI: 1.12, 1.3) per doubling of the Cd body burden. The respective risk of having albuminuria increased 2.95-fold (p = 0.042) and 4.17-fold (p = 0.020) in subjects who had hypertension plus severe and extremely severe tubular dysfunction, defined according to the elevated β2M excretion rates. In multiple regression analysis, the Ealb/Ccr increased linearly with both the systolic blood pressure (SBP, β = 0.263) and diastolic blood pressure (DBP, β = 0.150), while showing an inverse association with eGFR (β = -0.180). The mediation model analyses inferred that a declining eGFR induced by Cd contributed to 80.6% of the SBP increment (p = 0.005), which then fully mediated an elevation of albumin excretion (p < 0.001). The present study provides, for the first time, evidence that causally links Cd-induced eGFR reductions to blood pressure elevations, which enhance albumin excretion.

Organic and inorganic chemicals co-occur in household dust, and these chemicals have been determined to have endocrine and metabolic disrupting effects. While there is increasing study of chemical mixtures, the effects of complex mixtures mimicking household dust and other environmental matrices have not been well studied and their potential metabolism disrupting effects are thus poorly understood. Previous research has demonstrated high potency adipogenic effects of residential household dust extracts using in vitro adipogenesis assays. More recent research simplified this to a mixture relevant to household dust and comprised of common co-occurring organic and inorganic contaminants, finding that these complex combinations often exhibited additive or even synergistic effects in cell models. This study aimed to translate our previous in vitro observation to an in vivo model, the developing zebrafish, to evaluate the metabolic effects of early exposure to organic and inorganic chemicals, individually and in mixtures. Zebrafish embryos were exposed from 1 day post fertilization (dpf) to 6 dpf, then metabolic energy expenditure, swimming behavior and gene expression were measured. Globally, we observed that most mixtures did not reflect the effects of individual chemicals; the BFR mixture produced a less potent effect when compared to the individual chemicals, while the PFAS and the inorganic mixtures seemed to have a more potent effect than the individual chemicals. Finally, the environmental mixture, mimicking household dust proportions, was less potent than the inorganic chemical mix alone. Additional work is necessary to better understand the mixture effect of inorganic and organic chemicals combined.

Exposure to even low levels of the environmental pollutant cadmium (Cd) increases the risk of kidney damage and malfunction. The body burden of Cd at which these outcomes occur is not, however, reliably defined. Here, multiple-regression and mediation analyses were applied to data from 737 non-diabetic Thai nationals, of which 9.1% had an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 (a low eGFR). The excretion of Cd (ECd), and renal-effect biomarkers, namely β2-microglobulin (Eβ2M), albumin (Ealb), and N-acetylglucosaminidase (ENAG), were normalized to creatinine clearance (Ccr) as ECd/Ccr Eβ2M/Ccr, Ealb/Ccr, and ENAG/Ccr. After adjustment for potential confounders, the risks of having a low eGFR and albuminuria rose twofold per doubling ECd/Ccr rates and they both varied directly with the severity of β2-microglobulinuria. Doubling ECd/Ccr rates also increased the risk of having a severe tubular injury, evident from ENAG/Ccr increments [POR = 4.80, p = 0.015]. ENAG/Ccr was strongly associated with ECd/Ccr in both men (β = 0.447) and women (β = 0.394), while showing a moderate inverse association with eGFR only in women (β = -0.178). A moderate association of ENAG/Ccr and ECd/Ccr was found in the low- (β = 0.287), and the high-Cd body burden groups (β = 0.145), but ENAG/Ccr was inversely associated with eGFR only in the high-Cd body burden group (β = -0.223). These discrepancies together with mediation analysis suggest that Cd-induced nephron destruction, which reduces GFR and the tubular release of NAG by Cd, involves different mechanisms and kinetics.

Since even low-level environmental exposure to cadmium (Cd) can lead to numerous unfavourable health outcomes, including damage to the nervous system, it is important to recognize the risk of health damage by this xenobiotic, the mechanisms of its toxic influence, and to find an effective protective strategy. This study aimed to evaluate, in a female Wistar rat model of current human environmental exposure to Cd (1 and 5 mg/kg of diet for 3-24 months), if the low-to-moderate treatment with this element can harm the brain and whether the supplementation with a 0.1% Aronia melanocarpa L. (Michx.) Elliott berries (chokeberries) extract (AE) can protect against this effect. The exposure to Cd modified the values of various biomarkers of neurotoxicity, including enzymes (acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), phospholipase A2 (PLA2), and nitric oxide synthase 1 (NOS1)) and non-enzymatic proteins (calmodulin (CAM), nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (KEAP1)) crucial for the functioning of the nervous system, as well as the concentrations of calcium (Ca) and magnesium (Mg) and some metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the brain tissue. The co-administration of AE, partially or entirely, protected from most of the Cd-induced changes alleviating its neurotoxic influence. In conclusion, even low-level chronic exposure to Cd may adversely affect the nervous system, whereas the supplementation with A. melanocarpa berries products during the treatment seems a protective strategy.

Edible offal of farmed animals can accumulate cadmium (Cd). However, no studies have investigated Cd bioavailability and its health effects. Here, based on mouse models, market pork kidney samples exhibited high Cd relative bioavailability of 74.5 ± 11.2% (n = 26), close to 83.8 ± 7.80% in Cd-rice (n = 5). This was mainly due to high vitamin D3 content in pork kidney, causing 1.7-2.3-fold up-regulated expression of duodenal Ca transporter genes in mice fed pork kidney compared to mice fed Cd-rice, favoring Cd intestinal absorption via Ca transporters. However, although pork kidney was high in Cd bioavailability, subchronic low-dose (5% in diet) consumption of two pork kidney samples having 0.48 and 0.97 μg Cd g-1 dw over 35 d did not lead to significant Cd accumulation in the tissue of mice fed Cd-free rice but instead remarkably decreased Cd accumulation in the tissue of mice fed Cd-rice (0.48 μg Cd g-1) by ∼50% and increased abundance of gut probiotics (Faecalibaculum and Lactobacillus). Overall, this study contributed to our understanding of the bioavailability and health effects associated with Cd in edible offal, providing mechanistic insights into pork kidney consumption safety based on Cd bioavailability.

Rice (Oryza sativa) is an important nutritional grain for the majority of Asian countries, but it is also a major source of cadmium (Cd) accumulation. A pot experiment was carried out to investigate the Cd uptake and translocation of high Cd (IR-50) and low Cd (White Ponni) rice cultivars in Cd-contaminated soils. The findings revealed that Cd impacts on rice development and growth differed depending on rice cultivars. Soil Cd levels in the seedling stage exceeded the critical levels (3-6 mg kg-1) only 5.0 mg kg-1 Cd treatment for the IR-50 (7.47 mg kg-1). At higher Cd treatments (1.0 and 5.0 mg kg-1), morphometric characteristics and yield of grains showed a declining and increasing trend in both rice varieties, respectively. The accumulation of Cd was higher in soil and roots during seedling and tillering stages, whereas in booting and maturity stages increased in stems and leaves in IR-50 and WP rice varieties. Cd levels in rice grains above the maximum allowable limit (0.4 mg kg-1) only in IR-50 (0.51 mg kg-1) rice cultivar at maturity stage. The EF of Cd were classified as minor enrichment to 'moderate enrichment' in both rice cultivars. TF values exhibited > 1 in booting and maturity stages in both rice cultivars at higher Cd treatments. The study concluded that the IR-50 rice variety exhibited increased Cd intake and transported to various parts of rice plants, particularly grains. The findings indicate that WP rice cultivar is more resistant to Cd toxicity, reducing health hazards for persons who preferred the staple food rice.

Biochar obtained via microwave-assisted pyrolysis (MAP) at 720 W and 15 min from cocoa pod husk (CPH) is an efficient adsorbent of Cd2+(aq). Biochar of residual biomass of CPH (BCCPH) possesses favorable physicochemical and morphological properties, featuring a modest surface area yet a suitable porous structure. Adsorption, predominantly governed by physisorption, is influenced by the oxygen-containing active sites (-COOR, -C(R)O, and -CH2OR; R = H, alkyl). CdCO3 formation occurs during adsorption. Experimental data were well-fitted into various kinetic models for a broad understanding of the sorption process. Langmuir model indicates a maximum adsorption capacity of 14.694 mg/g. The thermodynamic study confirms the spontaneous and endothermic sorption. Studies at the molecular level have revealed that the Cd2+ ion tends to bind to surface aromatic carbon atoms. This sustainable approach produces BCCPH via MAP as a solution for waste transformation into water-cleaning materials.

Metals are integral components of the natural environment, and their presence in the food supply is inevitable and complex. While essential metals such as sodium, potassium, magnesium, calcium, iron, zinc, and copper are crucial for various physiological functions and must be consumed through the diet, others, like lead, mercury, and cadmium, are toxic even at low concentrations and pose serious health risks. This study comprehensively analyzes the presence, importance, and consequences of metals in the food chain. We explore the pathways through which metals enter the food supply, their distribution across different food types, and the associated health implications. By examining current regulatory standards for maximum allowable levels of various metals, we highlight the importance of ensuring food safety and protecting public health. Furthermore, this research underscores the need for continuous monitoring and management of metal content in food, especially as global agricultural and food production practices evolve. Our findings aim to inform dietary recommendations, food fortification strategies, and regulatory policies, ultimately contributing to safer and more nutritionally balanced diets.

The objective of the present review is to discuss epidemiological evidence demonstrating the association between toxic metal (Cd, Pb, Hg, As, Sn, Ti, Tl) exposure and retinal pathology, along with the potential underlying molecular mechanisms. Epidemiological studies demonstrate that Cd, and to a lesser extent Pb exposure, are associated with age-related macular degeneration (AMD), while the existing evidence on the levels of these metals in patients with diabetic retinopathy is scarce. Epidemiological data on the association between other toxic metals and metalloids including mercury (Hg) and arsenic (As), are limited. Clinical reports and laboratory in vivo studies have shown structural alterations in different layers of retina following metal exposure. Examination of retina samples demonstrate that toxic metals can accumulate in the retina, and the rate of accumulation appears to increase with age. Experimental studies in vivo and in vitro studies in APRE-19 and D407 cells demonstrate that toxic metal exposure may cause retinal damage through oxidative stress, apoptosis, DNA damage, mitochondrial dysfunction, endoplasmic reticulum stress, impaired retinogenesis, and retinal inflammation. However, further epidemiological as well as laboratory studies are required for understanding the underlying molecular mechanisms and identifying of the potential therapeutic targets and estimation of the dose-response effects.

The quantification of arsenic, mercury, cadmium and lead in the human bloodstream is routinely used today to assess exposure to these toxic metal(loid)s, but the interpretation of the obtained data in terms of their cumulative health relevance remains problematic. Seemingly unrelated to this, epidemiological studies strongly suggest that the simultaneous chronic exposure to these environmental pollutants is associated with the etiology of autism, type 2 diabetes, irritable bowel disease and other diseases. This from a public health point of view undesirable situation urgently requires research initiatives to establish functional connections between human exposure to multiple toxic metal(loid) species and adverse health effects. One way to establish causal exposure-response relationships is a molecular toxicology approach, which requires one to unravel the biomolecular mechanisms that unfold after individual toxic metal(loid)s enter the bloodstream/organ nexus as these interactions ultimately determine which metabolites impinge on target organs and thus provide mechanistic links to diseases of unknown etiology. In an attempt to underscore the importance of the toxicological chemistry of metal(loid)s in the bloodstream, this review summarizes recent progress into relevant bioinorganic processes that are implicated in the etiology of adverse organ-based health effects and possibly diseases. A better understanding of these bioinorganic processes will not only help to improve the regulatory framework to better protect humans from the adverse effects of toxic metal(loid) species, but also represents an important starting point for the development of treatments to ameliorate pollution-induced adverse health effects on human populations, including pregnant women, the fetus and children.

Cadmium (Cd) is a widespread environmental toxicant that poses significant threat to public health. After intake, Cd is distributed throughout the body via blood and lymphatic circulation. However, the effect of Cd on lymphatic vessels has not been revealed. In this study, mice were exposed to 10 μM cadmium chloride through drinking water immediately after corneal alkali burn. In vivo analyses showed that Cd treatment enhances the alkali burn-induced corneal lymphangiogenesis, which is characterized by increased expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), prospero-related homeobox 1 (PROX-1) and vascular endothelial growth factor receptor 3 (VEGFR3). In vitro, the proliferation and migration of human dermal lymphatic endothelial cells (HDLECs) are increased by 1 μM Cd treatment, while inhibited by 10 μM Cd treatment. At a concentration of 1 μM, Cd specifically induces phosphorylation of signal transducer and activator of transcription 3 (STAT3), but has no effect on the MAPK, AKT, or NF-κB signaling pathway. In the presence of the STAT3 inhibitor STATTIC, Cd fails to induce HDLECs proliferation and migration. In addition, Cd upregulates VEGFR3 expression and its gene promoter activity in a STAT3-dependent manner. Our study suggests that low-dose Cd promotes lymphangiogenesis through activation of the STAT3 signaling pathway.

Zinc (Zn) is the second most abundant metal in the human body and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from the diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself and then the quantity of other food constituents such as phytate, protein, and calcium (Ca). In cells, Zn is involved in the regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. The cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, solute-linked carriers 30A and 39A (SLC30A and SLC39A), known as the ZnT and Zrt/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to Zn intake levels that may lower the risk of vision loss and bone fracture associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels.

Cadmium (Cd) is a highly toxic metal that frequently contaminates our environment. In this study, the bioflocculant-producing, cadmium-resistant Escherichia fergusonii ZSF-15 was characterized from Paharang drain, Bawa Chak, Faisalabad, Pakistan. The Cd-resistant E. fergusonii was used to determine the bioflocculant production using yeast-peptone-glycerol medium (pH 6.5) supplemented with 50 mg L-1 of Cd. The culture was incubated for 3 days at 37 °C in a rotary shaker at 120 rpm. The fermentation broth was centrifuged at 4000 g for 10 min after the incubation period. The maximum flocculating activity by isolate ZSF-15 was found to be 71.4% after 48 h of incubation. According to the Fourier transform infrared spectroscopy analysis, the bioflocculant produced by strain ZSF-15 was comprised of typical polysaccharide and protein, i.e. hydroxyl, carboxyl, and amino groups. The strain ZSF-15 exhibited bioflocculant activity at range of pH (6-8) and temperature (35-50℃). Maximum flocculation activity (i.e. 71%) was observed at 47℃, whereas 63% flocculation production was observed at pH 8. In the present study, antioxidant enzyme profile of ZSF-15 was also evaluated under cadmium stress. A significant increase in antioxidant enzymes including superoxide dismutase (118%) and ascorbate peroxidase (28%) was observed, whereas contents of catalase (86%), glutathione transferase (13%), and peroxidase (8%) were decreased as compared to control.

Heavy metals' presence as environmental pollutants has a close link to adverse health effects. Frailty, a clinical syndrome hallmarked by elevated vulnerability to stressors, presents a substantial challenge in healthcare. However, the association between exposure to heavy metals and frailty largely remains unexplored. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2003-2018 and correlated with the U.S. National Death Index (NDI) from 2019, we investigated mortality outcomes. Logistic regression, Cox regression, Kaplan-Meier survival curves, weighted quantile-sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were employed to assess the association between heavy metal exposure and frailty incidence and mortality in the frail population. Eight metals were measured in urine using inductively coupled plasma mass spectrometry with values adjusted for urinary creatinine, which was used to reflect heavy metal exposure. The cohort incorporated 5370 female participants aged 45 and above, with 1518 diagnosed with frailty. The findings indicated a substantial correlation between exposure to specific heavy metals, namely tungsten (odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.31-2.89), cobalt (OR: 1.64, 95% CI: 1.40-1.93), cadmium (OR: 1.93, 95% CI: 1.52-2.43), and uranium (OR: 7.36, 95% CI: 1.53-35.28), and an elevated risk of frailty. WQS and BKMR regression models identified cadmium, cobalt, and tungsten as main contributors to frailty. Cox regression analysis, after adjustment for covariates, suggested that the higher the exposure levels to cadmium and lead, the higher the risk of death in frail patients, with associated hazard ratios (HR) of 95% CI: 1.96 (1.53, 2.52) and 1.30 (1.13, 1.49), respectively. Our study revealed a significant positive correlation between exposure to heavy metal mixtures and frailty onset in middle-aged and older adults, along with increased mortality in frail patients. Cobalt, cadmium, and tungsten emerged as prominent contributors to frailty, with cobalt and cadmium directly impacting the long-term life expectancy of frail patients.

Cadmium (Cd) is a metal with no nutritional value or physiological role. However, it is found in the body of most people because it is a contaminant of nearly all food types and is readily absorbed. The body burden of Cd is determined principally by its intestinal absorption rate as there is no mechanism for its elimination. Most acquired Cd accumulates within the kidney tubular cells, where its levels increase through to the age of 50 years but decline thereafter due to its release into the urine as the injured tubular cells die. This is associated with progressive kidney disease, which is signified by a sustained decline in the estimated glomerular filtration rate (eGFR) and albuminuria. Generally, reductions in eGFR after Cd exposure are irreversible, and are likely to decline further towards kidney failure if exposure persists. There is no evidence that the elimination of current environmental exposure can reverse these effects and no theoretical reason to believe that such a reversal is possible. This review aims to provide an update on urinary and blood Cd levels that were found to be associated with GFR loss and albuminuria in the general populations. A special emphasis is placed on the mechanisms underlying albumin excretion in Cd-exposed persons, and for an accurate measure of the doses-response relationships between Cd exposure and eGFR, its excretion rate must be normalised to creatinine clearance. The difficult challenge of establishing realistic Cd exposure guidelines such that human health is protected, is discussed.

The existing data demonstrate that probiotic supplementation affords protective effects against neurotoxicity of exogenous (e.g., metals, ethanol, propionic acid, aflatoxin B1, organic pollutants) and endogenous (e.g., LPS, glucose, Aβ, phospho-tau, α-synuclein) agents. Although the protective mechanisms of probiotic treatments differ between various neurotoxic agents, several key mechanisms at both the intestinal and brain levels seem inherent to all of them. Specifically, probiotic-induced improvement in gut microbiota diversity and taxonomic characteristics results in modulation of gut-derived metabolite production with increased secretion of SFCA. Moreover, modulation of gut microbiota results in inhibition of intestinal absorption of neurotoxic agents and their deposition in brain. Probiotics also maintain gut wall integrity and inhibit intestinal inflammation, thus reducing systemic levels of LPS. Centrally, probiotics ameliorate neurotoxin-induced neuroinflammation by decreasing LPS-induced TLR4/MyD88/NF-κB signaling and prevention of microglia activation. Neuroprotective mechanisms of probiotics also include inhibition of apoptosis and oxidative stress, at least partially by up-regulation of SIRT1 signaling. Moreover, probiotics reduce inhibitory effect of neurotoxic agents on BDNF expression, on neurogenesis, and on synaptic function. They can also reverse altered neurotransmitter metabolism and exert an antiamyloidogenic effect. The latter may be due to up-regulation of ADAM10 activity and down-regulation of presenilin 1 expression. Therefore, in view of the multiple mechanisms invoked for the neuroprotective effect of probiotics, as well as their high tolerance and safety, the use of probiotics should be considered as a therapeutic strategy for ameliorating adverse brain effects of various endogenous and exogenous agents.

The ongoing anthropogenic pollution of the biosphere with As, Cd, Hg and Pb will inevitably result in an increased influx of their corresponding toxic metal(loid) species into the bloodstream of human populations, including children and pregnant women. To delineate whether the measurable concentrations of these inorganic pollutants in the bloodstream are tolerable or implicated in the onset of environmental diseases urgently requires new insight into their dynamic bioinorganic chemistry in the bloodstream-organ system. Owing to the human exposure to multiple toxic metal(loid) species, the mechanism of chronic toxicity of each of these needs to be integrated into a framework to better define the underlying exposure-disease relationship. Accordingly, this review highlights some recent advances into the bioinorganic chemistry of the Cd2+, Hg2+ and CH3Hg+ in blood plasma, red blood cells and target organs and provides a first glimpse of their emerging mechanisms of chronic toxicity. Although many important knowledge gaps remain, it is essential to design experiments with the intent of refining these mechanisms to eventually establish a framework that may allow us to causally link the cumulative exposure of human populations to multiple toxic metal(loid) species with environmental diseases of unknown etiology that do not appear to have a genetic origin. Thus, researchers from a variety of scientific disciplines need to contribute to this interdisciplinary effort to rationally address this public health threat which may require the implementation of stronger regulatory requirements to improve planetary and human health, which are fundamentally intertwined.

Cadmium (Cd) is an environmental toxicant of worldwide public health significance. Diet is the main non-workplace Cd exposure source other than passive and active smoking. The intestinal absorption of Cd involves transporters for essential metals, notably iron and zinc. These transporters determine the Cd body burden because only a minuscule amount of Cd can be excreted each day. The International Agency for Research on Cancer listed Cd as a human lung carcinogen, but the current evidence suggests that the effects of Cd on cancer risk extend beyond the lung. A two-year bioassay demonstrated that Cd caused neoplasms in multiple tissues of mice. Also, several non-tumorigenic human cells transformed to malignant cells when they were exposed to a sublethal dose of Cd for a prolonged time. Cd does not directly damage DNA, but it influences gene expression through interactions with essential metals and various proteins. The present review highlights the epidemiological studies that connect an enhanced risk of various neoplastic diseases to chronic exposure to environmental Cd. Special emphasis is given to the impact of body iron stores on the absorption of Cd, and its implications for breast cancer prevention in highly susceptible groups of women. Resistance to cell death and other cancer phenotypes acquired during Cd-induced cancer cell transformation, under in vitro conditions, are briefly discussed. The potential role for the ZnT1 efflux transporter in the cellular acquisition of tolerance to Cd cytotoxicity is highlighted.

Several studies have shown associations between cadmium (Cd) exposure and an increased risk of fractures. However, the size of the risk is still unclear and proper adjustment for smoking is a challenge. The aim of this study was to quantify the association between dietary cadmium measured in blood and fracture risk in the general Swedish population through a large population-based case-control study in never-smokers.

The study included 2113 incident cases with osteoporosis-related fractures and the same number of age- and sex-matched controls in never-smokers from the Swedish population-based Malmö Diet and Cancer study cohort. Cd in blood (B-Cd) was analyzed at baseline (1991-1996). Incident osteoporosis-related fractures (of the hip, distal radius, and proximal humerus) up to the year 2014 were identified using the National Patient Register. Associations between B-Cd and fractures were analyzed using logistic regression.

Median B-Cd was 0.22 μg/L (P25 = 0.16, P75 = 0.31) among 2103 cases and 0.21 (P25 = 0.15, P75 = 0.30) among 2105 controls. The risk of fracture was significantly increased (OR 1.58; 95 % confidence interval 1.08-2.31, per μg/L of B-Cd), after adjustment for age, sex, BMI, physical activity, and fiber consumption. In analyses by cadmium quartiles, the OR increased monotonically and was significant in the highest quartile of B-Cd (for B-Cd > 0.31 versus B-Cd < 0.15 μg/L; OR 1.21; 95 % confidence interval 1.01-1.45).

Even modestly increased blood cadmium in never-smokers is associated with increased risk of incident osteoporosis-related fractures.

Cadmium (Cd) is a pervasive toxic metal, present in most food types, cigarette smoke, and air. Most cells in the body will assimilate Cd, as its charge and ionic radius are similar to the essential metals, iron, zinc, and calcium (Fe, Zn, and Ca). Cd preferentially accumulates in the proximal tubular epithelium of the kidney, and is excreted in urine when these cells die. Thus, excretion of Cd reflects renal accumulation (body burden) and the current toxicity of Cd. The kidney is the only organ other than liver that produces and releases glucose into the circulation. Also, the kidney is responsible for filtration and the re-absorption of glucose. Cd is the least recognized diabetogenic substance although research performed in the 1980s demonstrated the diabetogenic effects of chronic oral Cd administration in neonatal rats. Approximately 10% of the global population are now living with diabetes and over 80% of these are overweight or obese. This association has fueled an intense search for any exogenous chemicals and lifestyle factors that could induce excessive weight gain. However, whilst epidemiological studies have clearly linked diabetes to Cd exposure, this appears to be independent of adiposity. This review highlights Cd exposure sources and levels associated with diabetes type 2 and the mechanisms by which Cd disrupts glucose metabolism. Special emphasis is on roles of the liver and kidney, and cellular stress responses and defenses, involving heme oxygenase-1 and -2 (HO-1 and HO-2). From heme degradation, both HO-1 and HO-2 release Fe, carbon monoxide, and a precursor substrate for producing a potent antioxidant, bilirubin. HO-2 appears to have also anti-diabetic and anti-obese actions. In old age, HO-2 deficient mice display a symptomatic spectrum of human diabetes, including hyperglycemia, insulin resistance, increased fat deposition, and hypertension.

Urinary cadmium excretion (ECd) rises with renal tissue content of the metal. Whereas glomerulopathies are sometimes associated with massive albuminuria, tubular accumulation of Cd typically causes modest albuminuria. Since β2-microglobulinuria (Eβ2M) is an established marker of proximal tubular dysfunction, we hypothesized that a comparison of albuminuria (Ealb) to Eβ2M in Cd-exposed subjects would provide evidence of similar mishandling of both proteins.

To depict excretion rates per functional nephron, ECd, Ealb, and Eβ2M were normalized to creatinine clearance (Ccr), a surrogate for the glomerular filtration rate (GFR). Estimation of GFR itself (eGFR) was accomplished with CKD-EPI formulas (2009). Linear and logistic regression analyses were performed to relate Ealb/Ccr, Eβ2M/Ccr, and eGFR to several independent variables. Simple linear regressions of eGFR, Ealb/Ccr, and Eβ2M/Ccr on ECd/Ccr were examined before and after adjustment of dependent variables for age. All regressions were performed after log-transformation of ratios and standardization of all variables. Increments in Ealb/Ccr and Eβ2M/Ccr and decrements in eGFR were quantified through four quartiles of ECd/Ccr.

As age or ECd/Ccr rose, Ealb/Ccr and Eβ2M/Ccr also rose, and eGFR fell. In linear regressions, slopes relating Ealb/Ccr and Eβ2M/Ccr to ECd/Ccr were similar. After adjustment of dependent variables for age, coefficients of determination (R2) for all regressions rose by a multiple, and slopes approached unity. Ealb/Ccr and Eβ2M/Ccr were similarly associated with each other. Mean Ealb/Ccr and Eβ2M/Ccr rose and mean eGFR fell in stepwise fashion through quartiles of ECd/Ccr. Whereas Eβ2M/Ccr did not vary with blood pressure, Ealb/Ccr rose in association with hypertension in two of the four quartiles.

Our data indicate that Cd in renal tissue affected tubular reabsorption of albumin and β2M similarly in a large cohort of exposed subjects. The results suggest that Cd reduced receptor-mediated endocytosis and subsequent lysosomal degradation of each protein by a shared mechanism.

Rising waste construction, agricultural actions, and manufacturing sewages all contribute to heavy metal accumulation in water resources. Humans consume heavy metals-contaminated substances to make sustenance, which equally ends up in the food circle. Cleaning of these vital properties, along with the prevention of new pollution, has long been required to evade negative strength consequences. Most wastewater treatment techniques are widely acknowledged to be costly and out of the grasp of governments and small pollution mitigation businesses. Utilizing hyper-accumulator plants that are extremely resilient to heavy metals in the environment/soil, phytoremediation is a practical and promising method for eliminating heavy metals from contaminated environments. This method extracts, degrades, or detoxifies harmful metals using green plants. The three phytoremediation techniques of phytostabilization, phytoextraction, and phytovolatilization have been used extensively for soil remediation. Regarding their ability to be used on a wide scale, conventional phytoremediation methods have significant limitations. Hence, biotechnological attempts to change plants for heavy metal phytoremediation methods are extensively investigated in order to increase plant effectiveness and possible use of improved phytoremediation approaches in the country of India. This review focuses on the advances and significance of phytoremediation accompanied by the removal of various harmful heavy metal contaminants. Similarly, sources, heavy metals status in India, impacts on nature and human health, and variables influencing the phytoremediation of heavy metals have all been covered.

Chronic cadmium (Cd) exposure causes severe adverse health effects on the human body, especially the kidney tissue. Studies have demonstrated oxidative stress to be involved in renal pathological variations after exposure to Cd, but few effective treatments are available for the disease yet. Therefore, the present study was carried out to investigate the potential therapeutic intervention and its underlying molecular mechanisms of melatonin (MT), a natural antioxidant with multiple biological activities, against renal injury caused by Cd exposure in mice. C57BL/6 male mice (eight-week-old) were intragastrically administered with CdCl2, MT, or both for 30 days. Biochemical analysis showed that MT intervention significantly improved the SOD, GSH, and CAT activities while markedly decreasing the kidney MDA content of the mice exposed to Cd. Histological examination indicated that Cd exposure resulted in the atrophy of the renal glomerular, the degeneration and dilation of tubules, and the accumulation of fibrocytes. By contrast, MT administration effectively ameliorated the histological outcome of the injured kidney tissue. Moreover, administrating MT significantly inhibited proinflammatory cytokines TNF-α and iNOS expression in Cd-treated mice. Further, MT treatment markedly suppressed the expressions of renal fibrosis-related factors TGF-β1, α-SMA, and collagen Ⅰ in the injured renal tissue and the accumulation and development of renal fibrosis. In addition, the administration of MT significantly reduced the expression of caspase-3 and cell apoptotic death in the kidney tissue of Cd-exposed mice. In all, the data showed that MT has a compelling therapeutic potential in alleviating the pathological variations of renal injury caused by Cd exposure.

Cadmium (Cd) is a pervasive, toxic environmental pollutant that preferentially accumulates in the tubular epithelium of the kidney. Current evidence suggests that the cumulative burden of Cd here leads to the progressive loss of the glomerular filtration rate (GFR). In this study, we have quantified changes in estimated GFR (eGFR) and albumin excretion (Ealb) according to the levels of blood Cd ([Cd]b) and excretion of Cd (ECd) after adjustment for confounders. ECd and Ealb were normalized to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr. Among 482 residents of Cd-polluted and non-polluted regions of Thailand, 8.1% had low eGFR and 16.9% had albuminuria (Ealb/Ccr) × 100 ≥ 20 mg/L filtrate. In the low Cd burden group, (ECd/Ccr) × 100 < 1.44 µg/L filtrate, eGFR did not correlate with ECd/Ccr (β = 0.007) while an inverse association with ECd/Ccr was found in the medium (β = -0.230) and high burden groups (β = -0.349). Prevalence odds ratios (POR) for low eGFR were increased in the medium (POR 8.26) and high Cd burden groups (POR 3.64). Also, eGFR explained a significant proportion of Ealb/Ccr variation among those with middle (η2 0.093) and high [Cd]b tertiles (η2 0.132) but did not with low tertiles (η2 0.001). With an adjustment of eGFR, age and BMI, the POR values for albuminuria were increased in the middle (POR 2.36) and high [Cd]b tertiles (POR 2.74) and those with diabetes (POR 6.02) and hypertension (2.05). These data indicate that (ECd/Ccr) × 100 of 1.44 µg/L filtrate (0.01-0.02 µg/g creatinine) may serve as a Cd threshold level based on which protective exposure guidelines should be formulated.

The excretion of β₂-microglobulin (β₂M) above 300 µg/g creatinine, termed tubulopathy, was regarded as the critical effect of chronic exposure to the metal pollutant cadmium (Cd). However, current evidence suggests that Cd may induce nephron atrophy, resulting in a reduction in the estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m². Herein, these pathologies were investigated in relation to Cd exposure, smoking, diabetes, and hypertension. The data were collected from 448 residents of Cd-polluted and non-polluted regions of Thailand. The body burden of Cd, indicated by the mean Cd excretion (E_Cd), normalized to creatinine clearance (C_cr) as (E_Cd/C_cr) × 100 in women and men did not differ (3.21 vs. 3.12 µg/L filtrate). After adjustment of the confounding factors, the prevalence odds ratio (POR) for tubulopathy and a reduced eGFR were increased by 1.9-fold and 3.2-fold for every 10-fold rise in the Cd body burden. In women only, a dose-effect relationship was seen between β₂M excretion (E_β2M/C_cr) and E_Cd/C_cr (F = 3.431, η² 0.021). In men, E_β2M/C_cr was associated with diabetes (β = 0.279). In both genders, the eGFR was inversely associated with E_β2M/C_cr. The respective covariate-adjusted mean eGFR values were 16.5 and 12.3 mL/min/1.73 m² lower in women and men who had severe tubulopathy ((E_β2M/C_cr) × 100 ≥ 1000 µg/L filtrate). These findings indicate that women were particularly susceptible to the nephrotoxicity of Cd, and that the increment of E_β2M/C_cr could be attributable mostly to Cd-induced impairment in the tubular reabsorption of the protein together with Cd-induced nephron loss, which is evident from an inverse relationship between E_β2M/C_cr and the eGFR.

Kidney disease associated with chronic cadmium (Cd) exposure is primarily due to proximal tubule cell damage. This results in a sustained decline in glomerular filtration rate (GFR) and tubular proteinuria. Similarly, diabetic kidney disease (DKD) is marked by albuminuria and a declining GFR and both may eventually lead to kidney failure. The progression to kidney disease in diabetics exposed to Cd has rarely been reported. Herein, we assessed Cd exposure and the severity of tubular proteinuria and albuminuria in 88 diabetics and 88 controls, matched by age, gender and locality. The overall mean blood and Cd excretion normalized to creatinine clearance (C_cr) as E_Cd/C_cr were 0.59 µg/L and 0.0084 µg/L filtrate (0.96 µg/g creatinine), respectively. Tubular dysfunction, assessed by β₂-microglobulin excretion rate normalized to C_cr(E_β2M/C_cr) was associated with both diabetes and Cd exposure. Doubling of Cd body burden, hypertension and a reduced estimated GFR (eGFR) increased the risks for a severe tubular dysfunction by 1.3-fold, 2.6-fold, and 84-fold, respectively. Albuminuria did not show a significant association with E_Cd/C_cr, but hypertension and eGFR did. Hypertension and a reduced eGFR were associated with a 3-fold and 4-fold increases in risk of albuminuria. These findings suggest that even low levels of Cd exposure exacerbate progression of kidney disease in diabetics.

The global prevalence of diabetes, and its major complication, diabetic nephropathy, have reached epidemic proportions. The toxic metal cadmium (Cd) also induces nephropathy, indicated by a sustained reduction in the estimated glomerular filtration rate (eGFR) and the excretion of β₂-microglobulin (β₂M) above 300 µg/day, which reflects kidney tubular dysfunction. However, little is known about the nephrotoxicity of Cd in the diabetic population. Here, we compared Cd exposure, eGFR, and tubular dysfunction in both diabetics (n = 81) and non-diabetics (n = 593) who were residents in low- and high-Cd exposure areas of Thailand. We normalized the Cd and β₂M excretion rates (E_Cd and E_β2M) to creatinine clearance (C_cr) as E_Cd/C_cr and E_β2M/C_cr. Tubular dysfunction and a reduced eGFR were, respectively, 8.7-fold (p < 0.001) and 3-fold (p = 0.012) more prevalent in the diabetic than the non-diabetic groups. The doubling of E_Cd/C_cr increased the prevalence odds ratios for a reduced eGFR and tubular dysfunction by 50% (p < 0.001) and 15% (p = 0.002), respectively. In a regression model analysis of diabetics from the low-exposure locality, E_β2M/C_cr was associated with E_Cd/C_cr (β = 0.375, p = 0.001) and obesity (β = 0.273, p = 0.015). In the non-diabetic group, E_β2M/C_cr was associated with age (β = 0.458, p < 0.001) and E_Cd/C_cr (β = 0.269, p < 0.001). However, after adjustment for age, and body mass index (BMI), E_β2M/C_cr was higher in the diabetics than non-diabetics of similar E_Cd/C_cr ranges. Thus, tubular dysfunction was more severe in diabetics than non-diabetics of similar age, BMI, and Cd body burden.

Toxicity with heavy metals has proven to be a significant hazard with several health problems linked to it. Heavy metals bioaccumulate in living organisms, pollute the food chain, and possibly threaten the health of animals. Many industries, fertilizers, traffic, automobile, paint, groundwater, and animal feed are sources of contamination of heavy metals. Few metals, such as aluminum (Al), may be eliminated by the elimination processes, but other metals like lead (Pb), arsenic (As), and cadmium (Ca) accumulate in the body and food chain, leading to chronic toxicity in animals. Even if these metals have no biological purpose, their toxic effects are still present in some form that is damaging to the animal body and its appropriate functioning. Cadmium (Cd) and Pb have negative impacts on a number of physiological and biochemical processes when exposed to sub-lethal doses. The nephrotoxic effects of Pb, As, and Cd are well known, and high amounts of naturally occurring environmental metals as well as occupational populations with high exposures have an adverse relationship between kidney damage and toxic metal exposure. Metal toxicity is determined by the absorbed dosage, the route of exposure, and the duration of exposure, whether acute or chronic. This can lead to numerous disorders and can also result in excessive damage due to oxidative stress generated by free radical production. Heavy metals concentration can be decreased through various procedures including bioremediation, pyrolysis, phytoremediation, rhizofiltration, biochar, and thermal process. This review discusses few heavy metals, their toxicity mechanisms, and their health impacts on cattle with special emphasis on the kidneys.

Cadmium (Cd) is a toxic metal that accumulates in kidneys, especially in the proximal tubular epithelial cells, where virtually all proteins in the glomerular ultrafiltrate are reabsorbed. Here, we analyzed archived data on the estimated glomerular filtration rate (eGFR) and excretion rates of Cd (E_Cd), total protein (E_Prot), albumin (E_alb), β₂-microglobulin (E_β2M), and α1-microglobulin (E_α1M), which were recorded for residents of a Cd contamination area and a low-exposure control area of Thailand. Excretion of Cd and all proteins were normalized to creatinine clearance (C_cr) as E_Cd/C_cr and E_Prot/C_cr to correct for differences among subjects in the number of surviving nephrons. Low eGFR was defined as eGFR ≤ 60 mL/min/1.73 m², while proteinuria was indicted by E_Pro/C_cr ≥ 20 mg/L of filtrate. E_Prot/C_cr varied directly with E_Cd/C_cr (β = 0.263, p < 0.001) and age (β = 0.252, p < 0.001). In contrast, eGFR values were inversely associated with E_Cd/C_cr (β = -0.266, p < 0.001) and age (β = -0.558, p < 0.001). At E_Cd/C_cr > 8.28 ng/L of filtrate, the prevalence odds ratios for proteinuria and low eGFR were increased 4.6- and 5.1-fold, respectively (p < 0.001 for both parameters). Thus, the eGFR and tubular protein retrieval were both simultaneously diminished by Cd exposure. Of interest, E_Cd/C_cr was more closely correlated with E_Prot/C_cr (r = 0.507), E_β2M (r = 0.430), and E_α1M/C_cr (r = 0.364) than with E_Alb/C_cr (r = 0.152). These data suggest that Cd may differentially reduce the ability of tubular epithelial cells to reclaim proteins, resulting in preferential reabsorption of albumin.